title: Absence of Siglec-H in MCMV infection elevates interferon alpha production but does not enhance viral clearance.
abstract: Plasmacytoid dendritic cells (pDCs) express the I-type lectin receptor Siglec-H and produce interferon α (IFNα), a critical anti-viral cytokine during the acute phase of murine cytomegalovirus (MCMV) infection. The ligands and biological functions of Siglec-H still remain incompletely defined in vivo. Thus, we generated a novel bacterial artificial chromosome (BAC)-transgenic "pDCre" mouse which expresses Cre recombinase under the control of the Siglec-H promoter. By crossing these mice with a Rosa26 reporter strain, a representative fraction of Siglec-H⁺ pDCs is terminally labeled with red fluorescent protein (RFP). Interestingly, systemic MCMV infection of these mice causes the downregulation of Siglec-H surface expression. This decline occurs in a TLR9- and MyD88-dependent manner. To elucidate the functional role of Siglec-H during MCMV infection, we utilized a novel Siglec-H deficient mouse strain. In the absence of Siglec-H, the low infection rate of pDCs with MCMV remained unchanged, and pDC activation was still intact. Strikingly, Siglec-H deficiency induced a significant increase in serum IFNα levels following systemic MCMV infection. Although Siglec-H modulates anti-viral IFNα production, the control of viral replication was unchanged in vivo. The novel mouse models will be valuable to shed further light on pDC biology in future studies.
authors.affiliation: Institute for Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research: A Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
authors.forename: Franz
authors.initials: F
authors.lastname: Puttur
authors.forename: Catharina
authors.initials: C
authors.lastname: Arnold-Schrauf
authors.forename: Katharina
authors.initials: K
authors.lastname: Lahl
authors.forename: Gulhas
authors.initials: G
authors.lastname: Solmaz
authors.forename: Marc
authors.initials: M
authors.lastname: Lindenberg
authors.forename: Christian Thomas
authors.initials: CT
authors.lastname: Mayer
authors.forename: Melanie
authors.initials: M
authors.lastname: Gohmert
authors.forename: Maxine
authors.initials: M
authors.lastname: Swallow
authors.forename: Christopher
authors.initials: C
authors.lastname: van Helt
authors.forename: Heike
authors.initials: H
authors.lastname: Schmitt
authors.forename: Lars
authors.initials: L
authors.lastname: Nitschke
authors.forename: Bart N
authors.initials: BN
authors.lastname: Lambrecht
authors.forename: Roland
authors.initials: R
authors.lastname: Lang
authors.forename: Martin
authors.initials: M
authors.lastname: Messerle
authors.forename: Tim
authors.initials: T
authors.lastname: Sparwasser
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006566:Herpesviridae Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016898:Interferon-alpha / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D037102:Lectins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018448:Models, Immunological; D018146:Muromegalovirus / Q000502:physiology*; D010950:Plasma Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014779:Virus Replication / Q000235:genetics / Q000276:immunology
chemical_list: D016898:Interferon-alpha; D037102:Lectins; D011956:Receptors, Cell Surface; C510552:Siglech protein, mouse